Apparatus, system, and method of archival and retrieval of samples

ABSTRACT

A sample archive method and system implement a plurality of sample carriers configured to support a plurality of sample nodes in a predetermined spatial relationship, sample storage devices for selectively placing the plurality of sample carriers in an archive, and sample node removal apparatus for locating and removing selected ones of the plurality of sample nodes. Alternative embodiments are disclosed wherein the sample node removal apparatus comprises a laser and a mechanical clipping tool, which may be manually operated or automated. An optical component may be operative to detect the location of selected sample carriers in the archive, selected ones of the plurality of sample nodes, or both. A positioning component may position the sample node removal apparatus responsive to signals transmitted by the optical component. Various apparatus and methods of archiving samples and preparing the same for analysis are also disclosed.

[0001] The present application is related to non-provisional applicationSer. No. __/___,___, filed Nov. 2, 2001, entitled “SAMPLE CARRIER” andalso to non-provisional application Ser. No. __/___,___, filed Nov. 2,2001, entitled “ARCHIVE AND ANALYSIS SYSTEM AND METHOD” the disclosuresof which are hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

[0002] Aspects of the present invention relate generally to archival ofsample material, and more particularly to a system and method ofarchiving and retrieving biological or non-biological samples maintainedin desiccated form at a plurality of sample nodes on a carrier.

DESCRIPTION OF THE RELATED ART

[0003] In many applications such as pharmaceutical and medical research,law enforcement, and military identification, for example, it is oftendesirable to have access to numerous biological samples. Conventionalbiorepositories or other sample storage facilities utilize liquid or lowtemperature cryogenic systems for sample storage; these liquid andcryogenic systems are expensive both to create and to maintain.Additionally, current technology generally presents system operatorswith complicated and labor intensive maintenance and administrativeresponsibilities.

[0004] Specifically, the intricacies of cryogenic systems may typicallyoblige technicians, researchers, and system operators to engage incoordinated labor for weeks to retrieve and to prepare thousands ofdeoxyribonucleic acid (DNA) samples from whole blood. Accordingly,conventional approaches for archiving DNA in liquid or cryogenic statesare fundamentally inadequate to the extent that they do not accommodatehigh volume processing and sample throughput. Current research trendsrecognize benefits associated with systems and methods of archiving andretrieving biological and non-biological samples which may be capable ofprocessing thousands of samples per day; current technology, however, isinadequate to attain throughput at this level. In fact, current systemsand methods cannot attain processing throughput of one hundred or moresamples per day.

[0005] Although some small volume liquid-state DNA and blood archivaltechniques have been useful in the past, present methodologies are notcapable of supporting the increasing storage and retrieval ratesrequired as advancing genomics technology becomes more prevalent as aresearch and diagnostic tool. Since the traditional cryogenic-basedarchival format is difficult and expensive to automate, systems basedupon existing technology are generally not amenable to the highthroughput demands of the market.

[0006] Recently, biological research laboratory systems have beenproposed which incorporate archiving and retrieval of blood samples indry or desiccated form. Present systems are generally based uponmodifications or variations of known techniques for storing DNA or otherorganic samples on a suitable substrate such as filter paper; somesystems require, or substantially benefit from, soaking the substrate orpaper with chemical denaturants and detergents prior to use. In anyevent, however, existing desiccated sample archival systems are manuallyoperated or only partially automated, and hence do not meet the highvolume processing demands of the market. Additionally, these systemsemploy a mechanical punch or other tool which is operative to removesamples from substrates, typically by punching through or otherwisephysically engaging the substrate material. Consequently, these toolsnecessarily make contact with multiple samples during ordinary use.

[0007] In that regard, those of skill in the art will appreciate thateven if the current substrate-based archive systems were fullyautomated, significant cross contamination problems would undoubtedlyremain. During the sample removal punching process, extraneous fibersadhere to the punching tool or are otherwise released from thesubstrate, contaminating subsequent samples handled by the tool. Thesecontamination problems limit both the utility and the practicality oftraditional technologies. Moreover, the density of the storage facilityis ultimately limited by the inherent saturation limit of the substrate,as well as by the precision of mechanical and robotic components of thesystem.

[0008] In particular, full automation of the storage and retrievalprocesses in systems employing conventional filter paper or substratecard formats would necessarily require very precise robotics and othermachinery operating repeatedly to identify, to retrieve, and to replaceindividual storage cards within a large volume storage room or vault.Although precise, high-resolution robotic systems are currentlyavailable, finely tuned precision is achieved only when the mechanismsare operated within a small area. Accordingly, automating the storageand retrieval process for filter paper card or other substrate-basedarchival systems within an entire large scale vault is not a practicalsolution given current mechanical and robotic limitations.

SUMMARY

[0009] Embodiments of the present invention overcome variousshortcomings of conventional technology, providing a system and methodof automated archival and retrieval of desiccated biological ornon-biological samples. In accordance with one aspect of the invention,for example, a fully automated desiccated sample storage system may beoperative to achieve very high storage and retrieval rates, for example,greater than one hundred samples per day. An archive management systemmay include or support some or all of the following, inter alia: patientconsenting; questionnaire transcription; blood deposition; sample barcoding; archive storage; electronic sample browsing; sample retrieval;sample purification and extraction; and sample packaging and shipping.Coupled with the internet or other wide-area or local network, a fullyautomated archive facility may accommodate efficient search and timelytransport of biological or other samples, as well as attendant data andother information, throughout the world.

[0010] As set forth in detail below, the foregoing system and method mayemploy a desiccated sample carrier configured and operative tofacilitate efficient and timely access to contamination-free samples. Inaccordance with this aspect of the present invention, a sample carriermay accommodate very high sample densities at room temperature.Consequently, archive density may be satisfactory for high throughputdemands, while the expense and complications associated with cryogenicor liquid sample storage facilities may be reduced or eliminated.

[0011] In accordance with one aspect of the present invention, forexample, a sample carrier comprises a structural array and a pluralityof sample nodes; each of the plurality of sample nodes being removablyattached to the structural array at a respective attachment point andoperative to carry a discrete sample. In some embodiments, each of theplurality of sample nodes is operative to carry a biological sample,including proteins, polynucleotides, and DNA; in some alternativeembodiments, each of the plurality of sample nodes is operative to carrya non-biological sample.

[0012] In accordance with another aspect of the present invention, thesample carrier further comprises identifying indicia, some of which aredecipherable by an optical sensor. In some embodiments, each of theplurality of sample nodes comprises an associated transceiver operativeto transmit a unique signal; additionally, the associated transceivermay be operative to receive a control signal from a remote device.

[0013] Depending upon, inter alia, the type of sample and overall systemrequirements of the various embodiments, each of the plurality of samplenodes is solid or porous. Sample carrier embodiments are disclosedwherein each of the plurality of sample nodes comprises a sample supportmedium, which may comprise cellulose, a polymer such as polystyrene, orother material. In accordance with some embodiments, the sample supportmedium is derivatized, and may be positively charged or negativelycharged.

[0014] In another embodiment a sample carrier comprises a plurality ofstructural arrays supported in a predetermined spatial relationship anda plurality of sample nodes, wherein each of the plurality of samplenodes is removably attached to one of the plurality of structural arraysat a respective attachment point and operative to carry a discretesample. An alternative is disclosed wherein each of the plurality ofstructural arrays is supported in a predetermined spatial relationshiprelative to a respective sample container, such as a respective well ofa multi-well plate.

[0015] In the foregoing embodiment employing a plurality of structuralarrays, all of the alternatives and features mentioned above withreference to the single structural array embodiment are incorporated.

[0016] In accordance with another aspect of the present invention, amethod of transferring a specimen to a sample carrier comprisesproviding a sample carrier comprising a structural array supporting aplurality of sample nodes, and contacting the plurality of sample nodesto the specimen. Various alternatives are disclosed wherein the specimenis solid, gaseous, and liquid in form.

[0017] In some embodiments, the method further comprises selectivelyapplying a preservative to the plurality of sample nodes subsequent tothe contacting; it may be desirable that the preservative is operativeto desiccate the specimen transferred to the plurality of sample nodes.

[0018] The method may further comprise washing the plurality of samplenodes subsequent to the contacting. Additionally or alternatively, asnoted above, the method may further comprise allowing the plurality ofsample nodes to desiccate subsequent to the contacting, with or withoutthe assistance of a preservative.

[0019] In accordance with another aspect of the present invention, amethod of transferring specimens to a sample carrier comprises providinga sample carrier comprising a plurality of structural arrays, each ofthe plurality of structural arrays being supported in a predeterminedspatial relationship relative to a respective specimen container andsupporting a plurality of sample nodes, and contacting the plurality ofsample nodes supported by selected ones of the plurality of structuralarrays to a respective specimen. In some embodiments, the contactingcomprises bringing the plurality of sample nodes supported by each ofthe plurality of structural arrays into contact with a specimen in therespective specimen container.

[0020] In the foregoing embodiment employing a plurality of structuralarrays, all of the alternatives and features mentioned above withreference to the single structural array embodiment are incorporated.

[0021] In some embodiments, a sample carrier comprises: a structuralarray comprising a plurality of sample nodes, wherein each of theplurality of sample nodes is removably attached to the structural arrayat a respective attachment point and comprises a discrete sample supportmedium; and a specimen carried by the sample support medium at one ormore of the plurality of sample nodes.

[0022] In some embodiments, the specimen is biological, includingproteins, polynucleotides, and DNA; in some alternative embodiments, thespecimen is non-biological.

[0023] Depending upon, inter alia, the type of sample and overall systemrequirements of the various embodiments, the sample support medium issolid or porous. Sample carrier embodiments are disclosed wherein thesample support medium comprises cellulose, a polymer such aspolystyrene, or other material. In accordance with some embodiments, thesample support medium is derivatized or treated with a chemicalcompound, and may be positively charged or negatively charged.

[0024] In accordance with another aspect of the invention, a samplearchive system comprises a plurality of sample carriers configured tosupport a plurality of sample nodes in a predetermined spatialrelationship, sample storage means for selectively placing the pluralityof sample carriers in an archive, and sample node removal means forlocating and removing selected ones of the plurality of sample nodes.Alternative embodiments are disclosed wherein the sample node removalmeans comprises a laser and a mechanical clipping tool.

[0025] In some embodiments, the system comprises an optical componentoperative to detect the location of the selected ones of the pluralityof sample nodes; it may be desirable that such a system furthercomprises a positioning component operative to position the sample noderemoval means responsive to signals transmitted by the opticalcomponent.

[0026] In some embodiments, a sample archive system comprises aplurality of sample carrier receptacles, each of the plurality of samplecarrier receptacles configured to receive one or more sample carrierssupporting a plurality of sample nodes, a sample carrier storage deviceoperative to place selected ones of the one or more sample carriers inselected ones of the plurality of sample carrier receptacles, a samplecarrier location device operative to locate the selected ones of the oneor more sample carriers, a sample carrier retrieval device operative toretrieve the selected ones of the one or more sample carriers from onesof the plurality of sample carrier receptacles, and sample node removalmeans for identifying and removing selected ones of the plurality ofsample nodes.

[0027] In some embodiments, at least a portion of the plurality ofsample carrier receptacles includes a rack, while in other embodiments,at least a portion of the plurality of sample carrier receptaclesincludes a drawer. Embodiments of the system are disclosed wherein thesample carrier location device is a bar code reader. Additionally oralternatively, embodiments of the system are disclosed wherein thesample node removal means comprises a laser and a mechanical clippingtool.

[0028] A system is disclosed wherein the sample node removal meansfurther comprises an optical component operative to detect the locationof the selected ones of the plurality of sample nodes; in someembodiments, the sample node removal means may further comprise apositioning component operative to position a laser responsive tosignals transmitted by the optical component.

[0029] In some embodiments, it may be desirable that the system furthercomprise means for processing a sample supported by the selected ones ofthe plurality of sample nodes, or a controller for controlling operationof the sample carrier storage device and the sample carrier retrievaldevice.

[0030] In accordance with a further aspect of the present invention, asample archive system comprises an archive comprising a plurality ofsample carrier receptacles, each of the plurality of sample carrierreceptacles configured to receive one or more sample carriers supportinga plurality of sample nodes, and a robotics system comprising mechanismsoperative to store and to retrieve selected ones of the one or moresample carriers from the archive. The foregoing system may comprise asample carrier locator coupled to the robotics system and operative todetect a location of the selected ones of the one or more samplecarriers.

[0031] In some embodiments of the system, the sample carrier locatorcomprises an optical sensor; a system is further disclosed wherein therobotics system is automatically responsive to signals from the samplecarrier locator. As noted above, a system may further comprise a samplenode removal device operative to identify and to remove selected ones ofthe plurality of sample nodes from selected ones of the one or moresample carriers. A sample node locator coupled to the sample noderemoval device may be operative to detect a location of the selectedones of the plurality of sample nodes. Embodiments are disclosed whereinthe sample node removal device is automatically responsive to signalsfrom the sample node locator, which may comprise an optical sensor or arespective transceiver incorporated in each of the plurality of samplenodes. The system may include a sample carrier locator embodied in a barcode reader.

[0032] In some systems, the sample node removal device comprises amechanical clipping tool and a mechanical positioning system to positionthe mechanical clipping tool relative to the selected ones of theplurality of sample nodes, whereas in other systems, the sample noderemoval device comprises a laser and a mechanical positioning system toposition the laser relative to the selected ones of the plurality ofsample nodes. Embodiments are disclosed wherein the mechanicalpositioning system is operative to position the clipping tool or thelaser responsive to signals transmitted by an optical sensor. As notedabove, such systems may further comprise means for processing a samplesupported by the selected ones of the plurality of sample nodes. In somealternative embodiments, the system further comprises a computeroperative to control the robotics system and the sample node removaldevice.

[0033] In accordance with still another aspect of the present invention,a method of archiving samples comprises selectively transferring aspecimen to a plurality of discrete sample nodes attached to a samplecarrier, archiving the sample carrier in an archive facility, andrecording the location of the sample carrier in the archive facility.Embodiments of the foregoing method further comprise washing theplurality of discrete sample nodes subsequent to the selectivelytransferring, while other embodiments additionally or alternativelycomprise assigning identifying indicia, such as a bar code, for thesample carrier in accordance with the recording. The recording maycomprise writing data records associated with the plurality of discretesample nodes to a computer readable data storage medium.

[0034] Another method of archiving samples comprises obtaining aspecimen from a source, associating an identifier to the source and tothe specimen, writing the identifier and information associated with thesource and the specimen to a data structure, selectively transferringthe specimen to a plurality of discrete sample nodes attached to asample carrier and placing the sample carrier in a sample carrierreceptacle at an archive facility. The foregoing method may furthercomprise recording the location of the sample carrier in the archivefacility; additionally or alternatively, the method may further compriseacquiring consent to obtain the specimen.

[0035] In some embodiments, the method comprises assigning identifyingindicia, such as a bar code, for the sample carrier in accordance withthe associating and the selectively transferring. As noted above, therecording may comprise writing data records associated with theplurality of discrete sample nodes to a computer readable data storagemedium.

[0036] A computer readable medium is disclosed which is encoded withdata and computer executable instructions; the data and instructionscausing an apparatus executing the instructions to: receive informationregarding a sample and a source of the sample; assign an identifier tothe sample, the source, and the information; record the identifier andthe information in a data structure; and record the location within asample carrier of each of a plurality of discrete sample nodessupporting the sample.

[0037] The computer readable medium may further cause an apparatus totransmit control signals to a remote device at an archive facility.Additionally or alternatively, some embodiments of the computer readablemedium further cause an apparatus to transmit control signals to asample node removal device operative to locate and to remove selectedones of the plurality of discrete sample nodes, or to transmit controlsignals to a sample carrier storage device operative to place selectedones of a plurality of sample carriers in an archive. In the latterembodiment, the computer readable medium may additionally cause anapparatus to transmit control signals to a sample carrier retrievaldevice operative to retrieve the selected ones of the plurality ofsample carriers from the archive.

[0038] In accordance with one aspect of the present invention, a methodof preparing an archive sample for analysis comprises identifying asample to be analyzed, responsive to the identifying, ascertaining alocation of the sample on a discrete sample node supported by a samplecarrier, responsive to the ascertaining, removing the discrete samplenode from the sample carrier, and preparing the sample for analysis.

[0039] Embodiments of the foregoing method are disclosed wherein theidentifying comprises interrogating a data structure such as a database.In some embodiments, the ascertaining comprises utilizing an opticalsensor, which may include reading a bar code. Alternatively, theascertaining comprises identifying a unique signal transmitted from atransceiver attached to the discrete sample node; in this embodiment,the removing may comprise transmitting a control signal to thetransceiver.

[0040] As in the embodiments described above, methods are disclosedwherein the removing comprises utilizing a laser or a mechanicalclipping tool. The preparing may comprise depositing the discrete samplenode in a sample container; additionally or alternatively, the preparingmay comprise washing sample material attached to the discrete samplenode.

[0041] In the foregoing method, the composition of the sample (i.e.non-biological, biological, etc.) is as described above; accordingly,the method may further comprise amplifying a polynucleotide.

[0042] In some embodiments, a method of preparing an archive sample foranalysis comprises receiving a request related to an experiment,identifying a sample suitable for the experiment, responsive to thereceiving and the identifying, locating a sample carrier supporting thesample on a discrete sample node, detecting a location of the discretesample node on the sample carrier, removing the discrete sample nodefrom the sample carrier, and preparing the sample for analysis. As notedabove, the locating may comprise any or all of the following:interrogating a database maintaining records related to the samplecarrier; utilizing an optical sensor; and reading a bar code.

[0043] In accordance with one aspect of the method, the detectingcomprises obtaining video signals output from an optical sensor;accordingly, the removing may comprise automatically or manuallyoperating a sample node removal device responsive to the obtaining videosignals. Additionally or alternatively, the detecting comprisesidentifying a unique signal transmitted from a transceiver attached tothe discrete sample node; in this embodiment, the removing may comprisetransmitting a control signal to said transceiver.

[0044] In another embodiment, a sample node removal system comprises asample carrier configured to support a plurality of sample nodes in apredetermined spatial relationship, and node removal means for locatingand removing selected ones of said plurality of sample nodes. The noderemoval means may be embodied in the hardware, such as a laser or amechanical clipping tool, and computerized elements described above. Anoptical component may be operative to detect the location of theselected ones of the plurality of sample nodes; in some embodiments,signals output from the optical component may be used in conjunctionwith a positioning component operative to position the node removalmeans responsive to signals transmitted by said optical component. Asnoted above, such a system may further comprise a computer operative toreceive the signals and to control the positioning component and thenode removal means.

[0045] In another embodiment, a method of preparing an archive samplefor analysis comprises identifying a sample to be analyzed, responsiveto the identifying, obtaining the sample, preparing the sample foranalysis, and selectively repeating the identifying, the obtaining, andthe preparing at a rate sufficient to prepare in excess of 100 samplesfor analysis per day. As noted above, the identifying may compriseinterrogating a database, utilizing an optical sensor, or both. Theobtaining may comprise automatically or manually operating a sample noderemoval device, which may be a laser or a mechanical clipping tool.

[0046] Aspects of the methods previously discussed may be incorporatedinto the foregoing embodiment. Additionally, the selectively repeatingmay occur at a rate sufficient to prepare in excess of 200 samples foranalysis per day; methods are disclosed wherein the selectivelyrepeating occurs at a rate sufficient to prepare in excess of 500samples for analysis per day.

[0047] In some embodiments, a method of providing biological analyses toa remote client comprises maintaining a sample archive comprising aplurality of discrete sample nodes, receiving a request for a biologicalanalysis from a remote client, the request comprising identification ofa selected sample node from the plurality of discrete sample nodes andidentification of a selected assay, responsive to the receiving,retrieving the selected sample node from the archive and preparing theselected assay, and performing the selected assay for the selectedsample node.

[0048] The method of providing biological analyses may further comprisetransmitting results of the performing and data representative of theperforming to the remote client; the transmitting may include encryptingthe results and the data. In some embodiments, the method mayadditionally comprise shipping the selected sample node to the remoteclient. The request may be received via a network connection.

[0049] Embodiments of the foregoing method are disclosed wherein theassay is a genomics experiment or a proteomics experiment, for example,and wherein the retrieving the selected sample node comprises some orall of the following: interrogating a database; utilizing an opticalsensor; and automatically or manually operating a sample node removaldevice, which may comprise a laser or a mechanical clipping tool. Aswith the methods previously described, a method of providing biologicalanalyses may further comprise washing the sample prior to theperforming.

[0050] In accordance with another aspect of the invention, a method ofproviding samples to a remote client comprises maintaining a samplearchive comprising a plurality of discrete sample nodes, receiving arequest, via a network connection or otherwise, for a sample from aremote client, responsive to the receiving, identifying a selected oneof the plurality of discrete sample nodes in the archive, the selectedone of the plurality of discrete sample nodes carrying the sample,retrieving the selected one of the plurality of sample nodes from thearchive, and shipping the selected one of the plurality of sample nodesto the remote client.

[0051] In some embodiments, the method may further comprise performingan analysis of the sample prior to the shipping, and may additionallycomprise transmitting results of the performing and data representativeof the performing to the remote client. The above-mentioned shipping maycomprise packaging the selected one of the plurality of sample nodes ina sample container. As noted above, methods are disclosed furthercomprising washing the selected one of the plurality of sample nodesprior to said shipping.

[0052] The above-mentioned identifying may comprise interrogating adatabase, while the above-mentioned retrieving may comprise utilizing anoptical sensor, automatically or manually operating a sample noderemoval device, or both. The sample node removal device comprises alaser or a mechanical clipping tool, depending upon the embodiment andoverall system requirements, for example.

[0053] In some embodiments including performing an analysis of thesample, the analysis is a genomics experiment, whereas in otherembodiments, the analysis is a proteomics experiment.

[0054] In accordance with yet another aspect of the present invention, asystem comprises a sample archive comprising a plurality of samplecarriers, each of the plurality of sample carriers configured to supporta plurality of discrete sample nodes, a database containing data recordsassociated with ones of the plurality of discrete sample nodes and datarecords associated with biological analyses, means for receiving arequest from a remote client, the request containing information relatedto performing a selected analysis with selected ones of the plurality ofdiscrete sample nodes, a processor responsive to the means for receivingand operative to retrieve selected ones of the data records from thedatabase, a sample retrieval apparatus responsive to the processor andoperative to retrieve the selected ones of the plurality of discretesample nodes, an assay preparation apparatus responsive to the processorand operative to prepare an assay in accordance with the selectedanalysis, and means for conducting the selected analysis with theselected ones of the plurality of discrete sample nodes and forproviding results of the selected analysis to the processor.

[0055] Such a system may further comprise means for packaging theselected ones of the plurality of discrete sample nodes for shipping tothe remote client. Embodiments of the system are disclosed wherein thesample retrieval apparatus comprises a sample carrier locator operativeto detect a location of selected ones of the one or more samplecarriers. As noted above, the sample carrier locator may comprise anoptical sensor or a bar code reader. Embodiments of the system include asample retrieval apparatus comprising a sample node removal deviceoperative to remove the selected ones of the plurality of discretesample nodes from the plurality of sample carriers.

[0056] The sample retrieval apparatus may further comprise an opticalsensor; as described above with reference to other aspects of theinvention, embodiments of the foregoing system are disclosed wherein thesample node removal device is responsive to signals transmitted from theoptical sensor. The sample node removal device comprises a laser in someembodiments, and a mechanical clipping tool in others.

[0057] In some systems, the sample node removal device comprises a laserand a mechanical positioning system operative to position the laserrelative to the selected ones of the plurality of discrete sample nodesresponsive to the signals transmitted from an optical sensor;alternatively, the sample node removal device comprises a mechanicalclipping tool and a mechanical positioning system operative to positionthe mechanical clipping tool relative to the selected ones of theplurality of discrete sample nodes responsive to the signals transmittedfrom an optical sensor. As noted above, the sample node removal devicemay comprise a respective transceiver incorporated in each of theplurality of discrete sample nodes. In some embodiments, the analysisperformed by the system is a genomics experiment, and in otherembodiments, the analysis is a proteomics experiment.

[0058] A computer readable medium encoded with data and computerexecutable instructions is disclosed; the data and instructions causingan apparatus executing the instructions to receive a request from aremote client for performing a selected analysis of a selected samplenode maintained on a sample carrier in a sample archive, retrieve datarecords associated with the selected sample node and the selectedanalysis from a database, retrieve the selected sample node from thesample carrier, prepare an assay in accordance with the selectedanalysis, and conduct the selected analysis of a specimen carried on theselected sample node.

[0059] The computer readable medium may further cause an apparatus toprovide results of the selected analysis and data related to theselected analysis to the remote client. The computer readable medium mayfurther cause an apparatus to transmit control signals to a samplecarrier retrieval device operative to retrieve the sample carrier from asample carrier receptacle at an archive facility. Additionally, thiscomputer readable medium may further cause an apparatus to transmitcontrol signals to a sample carrier storage device operative to placethe sample carrier in the sample carrier receptacle. As set forth abovewith reference to computer readable media aspects, in some embodiments,a computer readable medium may further cause an apparatus to transmitcontrol signals to a sample node removal device operative to locate andto remove the selected sample node from the sample carrier.

[0060] In accordance with still another aspect of the present invention,a system comprises a sample archive, a database containing data recordsassociated with samples stored in the archive, means for receiving arequest from a remote client, the request containing information relatedto selected ones of the samples, a processor responsive to the means forreceiving and operative to retrieve selected ones of the data recordsfrom the database, a sample retrieval apparatus responsive to theprocessor and operative to retrieve the selected ones of the samples, asample preparation apparatus responsive to the processor and operativeto prepare the selected ones of the samples for analysis, and means forpackaging the selected ones of the samples for shipping to the remoteclient, wherein the sample retrieval apparatus, the sample preparationapparatus, and the means for packaging are operative at a ratesufficient to retrieve, to prepare, and to package in excess of 100samples per day.

[0061] The foregoing system may further comprise means for conducting aselected analysis, such as a genomics experiment or a proteomicsexperiment, for example, with the selected ones of the samples and forproviding results of the selected analysis to the processor.

[0062] As noted above, in some embodiments of the system, the sampleretrieval apparatus comprises some or all of the following: an opticalsensor, a laser, a mechanical clipping tool, or a transceiver.

[0063] In some embodiments, the sample retrieval apparatus, the samplepreparation apparatus, and the means for packaging are operative at arate sufficient to retrieve, to prepare, and to package in excess of 200samples per day; in still other embodiments, the rate may be sufficientto retrieve, to prepare, and to package in excess of 500 samples perday.

[0064] The foregoing and other aspects of various embodiments of thepresent invention will be apparent through examination of the followingdetailed description thereof in conjunction with the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0065]FIG. 1 is a simplified block diagram illustrating one embodimentof an automated sample archival and retrieval system.

[0066]FIG. 2 is a simplified block diagram illustrating the generaloperation of one embodiment of an automated sample archival andretrieval system.

[0067]FIG. 3 is a simplified block diagram illustrating components ofone embodiment of a sample archive facility and automated archivemanagement system.

[0068]FIG. 4A is a simplified diagram illustrating one embodiment of asample carrier.

[0069]FIG. 4B is a simplified partial longitudinal cross section of asample carrier constructed to engage a multi-well plate.

[0070]FIG. 4C is a simplified partial transverse cross section of asample carrier constructed to engage a multi-well plate.

[0071]FIG. 5A is a simplified diagrammatic plan view illustrating oneembodiment of a structural array employed by a sample carrier.

[0072]FIG. 5B is a simplified illustration of various embodiments of asample node.

[0073]FIG. 5C is a simplified block diagram illustrating one embodimentof a system and method of removing a sample node from a sample carrierstructural array.

[0074]FIG. 5D is a simplified block diagram illustrating anotherembodiment of a system and method of removing a sample node from asample carrier structural array.

[0075]FIG. 5E is a simplified block diagram illustrating one embodimentof a sample node identification or location system.

[0076] FIG: 6 is a simplified flow diagram illustrating one embodimentof a method of preparing an archive sample for analysis.

[0077]FIG. 7 is a simplified flow diagram illustrating one embodiment ofa sample archival method.

[0078]FIG. 8 is a simplified flow diagram illustrating one embodiment ofa method of retrieving and preparing an archive sample for analysis.

DETAILED DESCRIPTION

[0079] Turning now to the drawings, FIG. 1 is a simplified block diagramillustrating one embodiment of an automated sample archival andretrieval system. In the exemplary FIG. 1 embodiment, system 100generally comprises one or more remote computers or terminals, such asnetwork client 110, coupled to one or more servers, such as server 130,via a communications network 199. System 100 may also comprise datastorage media and peripheral equipment, represented by referencenumerals 141 and 120, respectively.

[0080] For clarity, only one server 130 and one client 110 have beendepicted in FIG. 1. Those of skill in the art will appreciate that thearrangement illustrated in FIG. 1 is presented for illustrative purposesonly, and that system 100 may be implemented with any number ofadditional servers, clients, or other components; the number and varietyof each device coupled to network 199 may vary in accordance with systemrequirements. In some embodiments, the functionality of one device, suchas peripheral device 120, for example, may reside on or be enabled byanother device, such as server 130.

[0081] In operation, client 110 may be capable of two-way datacommunication via communications network 199. In that regard, client 110may communicate with server 130, peripheral device 120, and data storagemedium 141 via network 199 or via one or more additional networks (notshown) which may be coupled to network 199. It will be appreciated bythose of skill in the art that client 110, server 130, and othercomponents depicted in FIG. 1 may be coupled via any number ofadditional networks without inventive faculty.

[0082] In some embodiments, client 110 may be a personal computer orworkstation, a personal digital assistant (PDA), a wireless telephone,or other network-enabled computing device, electronic apparatus, orcomputerized system. In operation, client 110 may execute software orother programming instructions encoded on a computer-readable storagemedium, and additionally may communicate with server 130, data storagemedium 141, and peripheral device 120 for monitor and controlapplications. For example, client 110 may interrogate server 130 andrequest transmission of data maintained at data storage medium 142coupled to, or accessible by, server 130. Additionally or alternatively,client 110 may transmit control signals or requests which may causedevice 120 to take some action or to execute a specified function orprogram routine.

[0083] It is well understood in the art that any number or variety ofperipheral equipment, such as device 120, may additionally be coupled tonetwork 199 without departing from the essence of the presentdisclosure. Examples of such peripheral devices include, but are notlimited to: servers; computers; workstations; terminals; input/outputdevices; laboratory equipment; printers; plotters; routers; bridges;cameras or video monitors; sensors; actuators; or any othernetwork-enabled device known in the art. Peripheral device 120 may becoupled to network 199 directly, as illustrated in FIG. 1, orindirectly, for example, through server 130, such that the functionalityor operation of device 120 may be influenced or controlled as describedbelow by hardware or software resident on server 130.

[0084] As is generally known in the art, server 130 may be embodied orimplemented in a single physical machine, for example, or in a pluralityof distributed but cooperating physical machines. In operation, server130 may incorporate all of the functionality of a file server orapplication server, and may additionally be coupled to data storagemedium 142 and sample archive facility 160.

[0085] In that regard, information and data records maintained at datastorage medium 142 and sample archive facility 160 may be accessible toclient 110 through bidirectional data communication with server 130 vianetwork 199.

[0086] Network 199 may be any communications network known in the artincluding, for example: the internet; a local area network (LAN); a widearea network (WAN); a Virtual Private Network (VPN); or any systemproviding data communication capability between client 110, server 130,storage medium 141, and peripheral device 120. In addition, network 199may be configured in accordance with any topology known in the art,including star, ring, bus, or any combination thereof.

[0087] By way of example, the data connection between components in FIG.1 may be implemented as a serial or parallel link. Alternatively, thedata connection may be any type generally known in the art forcommunicating or transmitting data across a computer network; examplesof such networking connections and protocols include, but are notlimited to: Transmission Control Protocol/Internet Protocol (TCP/IP);Ethernet; Fiber Distributed Data Interface (FDDI); ARCNET; token bus ortoken ring networks; Universal Serial Bus (USB) connections; andInstitute of Electrical and Electronics Engineers (IEEE) Standard 1394(typically referred to as “FireWire”) connections.

[0088] Other types of data network interfaces and protocols are withinthe scope and contemplation of the present disclosure. In particular,client 110 may be configured to transmit data to, and receive data from,other networked components using wireless data communication techniques,such as infrared (IR) or radio frequency (RF) signals, for example, orother forms of wireless communication. Accordingly, those of skill inthe art will appreciate that network 199 may be implemented as an RFPersonal Area Network (PAN).

[0089] Storage media 141,142 may be conventional read/write memory suchas a magnetic disk drive, a magneto-optical drive, an optical diskdrive, a floppy disk drive, a compact-disk read only memory (CD-ROM)drive, a digital versatile disk read only memory (DVD-ROM), a digitalversatile disk random access memory (DVD-RAM), transistor-based memory,or other computer-readable memory device for storing and retrievingdata.

[0090] Sample archive facility 160 may be arranged and configured tomaintain a multiplicity of biological or non-biological samples indesiccated form as set forth in more detail below. Additionally oralternatively, archive facility 160 may include mechanical and roboticsystems configured and operative to manipulate samples and to facilitatewashing, purification, testing, packaging, and shipping thereof. Varioustesting devices, experimental apparatus, and research equipment may haveaccess to the samples maintained at archive facility 160. Computerhardware and software resident at, or operatively coupled to mechanicaland other components at, archive facility 160 may communicate withserver 130 as illustrated in FIG. 1. In the exemplary FIG. 1 embodiment,archive facility 160 represents the foregoing samples, equipment,robotics, devices, and computer hardware and software, as well as anetwork interface enabling bi-directional data communication betweencomputer components in archive facility 160 and server 130.

[0091]FIG. 2 is a simplified block diagram illustrating the generaloperation of one embodiment of an automated sample archival andretrieval system. As illustrated in FIG. 2, client 210 may generallycorrespond to client 110 depicted and described above with reference toFIG. 1. Similarly, server 230, storage medium 242, and sample archivefacility 260 may correspond to server 130, storage medium 142, andarchive facility 160, respectively. The components in the FIG. 2arrangement may incorporate all of the respective functionality setforth above.

[0092] Responsive to requests or instructions from client 210, forexample, server 230 may be operative to retrieve data or informationfrom storage medium 242 and archive facility 260. Storage medium 242 maycomprise a database, for instance, or other data structure configured tomaintain data records and other information related to some or all ofthe following: the number and type of samples maintained in archivefacility 260; sample origins or sources; testing or research proceduresor protocols; operational parameters of various components incorporatedin archive facility 260; and access authorization, passwords, billinginformation, and the like associated with client 210. The foregoing listis provided by way of example only, and is not intended to be inclusive.

[0093] As illustrated in FIG. 2, storage medium 242 and archive facility260 may be configured to engage in two-way data communication such thatcomputer hardware or systems at archive facility 260 may read datarecords from, and write data to, storage medium 242. Alternatively, asillustrated and described below with reference to FIG. 3, various datastorage media may be incorporated in archive facility 260, for example.

[0094]FIG. 3 is a simplified block diagram illustrating components ofone embodiment of a sample archive facility and automated archivemanagement system. The exemplary FIG. 3 sample archive facility 360 maygenerally correspond to archive facilities 160 and 260 described abovewith reference to FIGS. 1 and 2, respectively, and may incorporate allof the functionality and operational characteristics set forth above.Archive facility 360 may generally comprise a system coordinationcomponent (coordinator) 310, a mechanical systems control component(controller) 320, and an archive and laboratory component (archive) 330.

[0095] System coordinator 310 may include computer hardware and softwareconfigured to manipulate or to instruct other system elements as setforth in detail below. Accordingly, coordinator 310 may be embodied in acomputer server or other electronic control system, for example, and maybe configured to run a multi-tasking operating system (OS 316) as isgenerally known in the art. Coordinator 310 generally comprises at leastone processor 311 coupled to other components described below via asystem bus (not shown). Processor 311 may be any microprocessor ormicrocontroller-based microcomputer known in the art.

[0096] The software code or programming instructions for controlling thefunctionality of processor 311 may be encoded in memory 312 or stored instorage medium 315. Memory 312 and storage medium 315 may be anycomputer-readable memory known in the art, as discussed above.Additionally or alternatively, some software or instruction code relatedto operation of processor 311 may reside at a remote device or storagemedium 242 as described above with reference to FIG. 2. Networkinterface hardware and software, such as represented by communicationinterface 319A and network software 317, respectively, may facilitatethe foregoing network communication, and may generally enable anyinterface known in the art for communicating or transferring filesacross a computer network as set forth in detail above.

[0097] Processor 311 may communicate via the system bus with a pluralityof peripheral equipment, including network interface 319A, for example,enabling two-way network data communications as described above.Additional peripheral equipment may be incorporated in or coupled tocoordinator 310; in some embodiments, such peripheral equipment mayinclude an input device 313 and an output device 314 enabling a systemadministrator, researcher, or other technician to interface withcoordinator 310 for monitor and control purposes. Examples of peripheralinput/output devices may include the following: conventional keyboards,keypads, trackballs, or other input devices; visual displays such ascathode ray tube (CRT) monitors, liquid crystal display (LCD) screens,touch-sensitive screens, or other monitor devices known in the art fordisplaying graphical images and text; microphones or other audio oracoustic sensor devices; audio speakers; and the like. It will beappreciated by those of skill in the art that peripheral equipment mayinclude suitable digital-to-analog and analog-to-digital conversioncircuitry (not shown), as appropriate.

[0098] In operation, coordinator 310, under control of processor 311 andOS 316, for example, may execute instruction code or applicationsoftware 318 configured and operative to provide desired functionalityfor archive facility 360 as a whole. In some embodiments, for instance,archive facility 360 may be configured to locate and to retrieveselected biological or non-biological samples and to prepare the samefor shipping to a remote site for experimentation or further storage.Additionally or alternatively, various components of archive facility360 may be employed to perform selected experiments with, or related to,retrieved samples. Overall functionality of archive facility 360 may beselectively altered or controlled in accordance with data and computerexecutable instructions, OS 316, and application software 318 undercontrol of processor 311. In an alternative embodiment, much of theautomated functionality of archive facility 360 described below may bemanual, or provided by a researcher or technician, for example.

[0099] Coordinator 310 may communicate with controller 320 via datasignals transmitted through communication interface 319B. In thatregard, controller 320 may incorporate a communication interface 329operative to enable bi-directional data communication with coordinator310. In one embodiment, the data interface between coordinator 310 andcontroller 320 may be implemented in the form of a wire-line (i.e.“hard-wired”), as represented by the double-headed arrow in FIG. 3. Byway of example, the data connection may be a serial, parallel, orEthernet link, or any other type of communication coupling, such asdescribed above, generally known in the art for communicating ortransmitting data across a computer network.

[0100] Other types of data interfaces and protocols are contemplated asdescribed above. In particular, as represented by the “lightning bolt”symbol in FIG. 3, coordinator 310 may be configured to transmit data to,and receive data from, controller 320 using wireless IR or RF signals,for example, or other forms of wireless communication. In a wirelessembodiment, coordinator 310 and controller 320 may be capable ofcommunicating via the Bluetooth(TM) standard, for example.

[0101] Controller 320 may additionally include a processor 321, memory322, and a mechanical interface 323; though not illustrated in the FIG.3 embodiment, controller 320 may additionally incorporate or be coupledto a data storage medium, which may store data and configurationinstructions related to overall operation of controller 320.

[0102] Software code, configuration information, or programminginstructions related to or influencing the functionality of processor321 may be encoded in memory 322, for example; additionally oralternatively, processor 321 may receive data and instructions fromcoordinator 310 via communication interface 329, or from an additionaldata source as described above.

[0103] In operation, controller 320 may transmit control signals orother data and instructions to affect operation of a device, apparatus,machine, robotic equipment, or other mechanism via mechanical interface323. The bidirectional data communication interface between controller320 and the apparatus to be controlled may generally correspond to thedata interfaces and protocols described above. As indicated in FIG. 3,controller 320 and the machinery to be monitored or controlled may becoupled via wire-line or wireless communication connections.

[0104] It will be appreciated that controller 320 may include one ormore additional mechanical interfaces 323, depending upon a variety offactors such as the number of mechanisms to be controlled, the overallcapabilities of processor 321, the capacity of memory 322, the datatransmission bandwidth of mechanical interface 323, and the desiredfunctionality of the archive facility 360, for example. Additionally oralternatively, archive facility 360 may comprise one or more additionalcontrollers operative to manipulate or to control additional mechanisms;in one embodiment, for example, each machine or device maintained atarchive facility 360 may be controlled by a respective dedicated controlcomponent such as controller 320.

[0105] In the FIG. 3 embodiment, robotic equipment or other mechanisms(robotics 331) to be monitored or controlled by controller 320 arerepresented as maintained or housed within archive 330. In addition torobotics 331 and associated computer hardware and software required foroperation thereof, archive 330 may generally comprise a biological ornon-biological sample archive (sample storage 332), instrumentation andequipment 333, and data storage medium 334.

[0106] As depicted in the high-level FIG. 3 block diagram, equipment 333generally represents a wide array of experimental apparatus andinstrumentation, laboratory supplies and functional paraphernalia, andthe like; the type, construction, and overall configuration of equipment333 maintained at archive 330 may be a function of the intendedoperational characteristics of archive facility 360, the state andorganization of the samples maintained in sample storage 332, and otherfactors. Examples of equipment 333 may include test tubes, microtiter orother multi-well plates, laboratory pipettes, storage vessels, shippingboxes and other packaging materials, scales or balances, and so forth.Those of skill in the art will appreciate that the scope of the presentdisclosure is not limited by the nature or characterization of equipment333, and that different types of apparatus may be required in accordancewith the desired functionality of archive facility 360.

[0107] In some embodiments, for example, archive facility 360 may serveas a large scale repository and source for biological or non-biologicalsamples; accordingly, equipment 333 in such an embodiment may includeappropriate containers or receptacles for accommodating samples duringshipping, packing material and shipping boxes or envelopes, scales orbalances for weighing samples or shipping materials, and so forth.Additionally or alternatively, archive facility 360 may be constructedand operative to serve as a central laboratory or experimental servicesprovider. In this latter embodiment, robotics 331 may includeproprietary or standardized laboratory modules dedicated to performingspecific experiments with biological and non-biological samples, forinstance, and equipment 333 may include pipettes and other liquidcontainers, microtiter plates constructed to receive multiple samples,antigens, reagents and other chemicals, and so forth.

[0108] Robotics 331 in the FIG. 3 embodiment of archive facility 360 mayrepresent a wide range of equipment and devices such as, for example:control modules implemented in computer hardware or software;computer-based or electronically controlled machinery, servos, hydraulicsystems, and the like; electronic circuits; peripheral equipment such asautoclaves, thermocyclers, or centrifuges; and any other devices to becontrolled by controller 320 via mechanical interface 323. In somebiological or non-biological sample archives, for example, robotics 331may be embodied in machine vision apparatus, optical sensors orscanners, bar code readers, and the like, which may identify particularsamples from among the plurality of samples in sample storage 332; thisidentification may be automatic, for example, or under control of anoperator or administrator through input/output devices 313,314 atcoordinator 310.

[0109] Various robotic or automated devices are known in the art forretrieving and transporting samples or sample carriers. Accordingly,robotics 331 may comprise automatically controlled arms or grippingdevices which may be translated or otherwise manipulated in threedimensions. Such robotics 331 may generally be configured and operativeto retrieve selected samples or sample carriers from sample storage 332and to manipulate retrieved sample carriers in accordance with data andinstructions received from processor 321 at controller 320. Those ofskill in the art will appreciate that robotics 331 may comprise computerhardware and software (not shown) sufficient to enable the bidirectionaldata communication illustrated in FIG. 3; additionally, some embodimentsof robotics 331 may include powerful processors, for example, coupled tomachine vision or other sample carrier identification devices such asbar code readers or optical sensors as described above.

[0110] In addition to placing, identifying, retrieving, and manipulatingsamples or sample carriers stored or archived at sample storage 332,robotics 331 may further be operative to utilize equipment 333 requiredfor conducting desired operations on or with respect to samples. Asnoted above, these operations may include washing, purification,alteration, testing or experimental analysis, replacing, packaging,shipping, and the like.

[0111] In that regard, robotics 331 may be embodied in, for example:sample storage devices or means operative to place samples or samplecarriers into receptacles at sample storage 332; sample locationdevices, which may employ optical sensors or machine vision technologyas described above, for locating particular samples or sample carriersfrom among the plurality archived at sample storage 332; sampleretrieval devices or means for retrieving selected sample carriers fromsample storage 332; and sample node removal devices, which also mayemploy optical sensors as described below. Alternatively, a technicianemployed at archive facility 360 may place sample carriers into samplecarrier receptacles, identify, locate and retrieve sample carriers, andmanipulate samples manually.

[0112] Data storage medium 334 may be embodied in the types of hardwaredescribed above, and may maintain data records related to the samplesdeposited in sample storage 332, operational parameters of robotics 331and other mechanized or automated devices, and the availability andvariety of equipment 333. For example, storage medium 334 may maintaindata records associated with each sample in sample storage 332,including, but not limited to: the nature or type of sample (e.g. blood,DNA, protein, environmental particles or pollutants); the source ororigin of the sample; the date the sample was archived; the number oftimes the sample has been retrieved; the tests or experiments conducted;and the like. Similarly, storage medium 334 may include data recordsrelated to the available supply of multi-well plates or other samplevessels at archive 330, the maintenance schedule for various roboticequipment, and so forth. It will be appreciated that data records andother information maintained at storage medium 334 may be transmitted tostorage medium 315 at coordinator 310; such transmission may occurperiodically, for example, at predetermined time intervals, orresponsive to specific requests or interrogations from processor 311.

[0113] The nature and variety of robotics 331 and equipment 333 employedat archive 330 may generally be influenced by the manner and form inwhich samples are maintained and stored in sample storage 332. Forexample, where samples are stored in conjunction with an identifying barcode label, robotics 331 may comprise a bar code reader. Since, as notedbriefly above, certain automated or other robotic systems are known forretrieving, handling, and replacing different types of laboratorycontainers and sample carriers, sample storage 332 may be constructedand configured for use with existing machines as set forth in moredetail below.

[0114] Sample storage 332 may generally comprise a plurality of samplecarrier receptacles, each of which may be configured to receive one ormore sample carriers. Sample carrier receptacles may be implemented asdrawers, shelves, or racks, for example. In some embodiments, samplestorage 332 may be an environmentally controlled vault or otherstructure designed to maintain samples at a constant or optimum humidityand temperature; environmental parameters may be selected in accordancewith the type and state of the samples. Alternatively, the entirearchive 330 may be contained within a single environmentally controlledvault.

[0115]FIG. 4A is a simplified diagram illustrating one embodiment of asample carrier. In the FIG. 4A embodiment, sample carrier 410 generallycomprises a frame structure having a longitudinal axis represented bythe dashed line 499. Carrier 410 may include one or more transverse(relative to longitudinal axis 499) members such as designated byreference numeral 412 and a plurality of sample site positioning members413, each of which may accommodate one or more sample site members414,415 in a predetermined spatial relationship. Though only threetransverse members 412 are illustrated in FIG. 4A, sample carrier 410may be scaled to include any number of additional transverse members 412as desired; alternatively, fewer than three transverse members 412 maybe appropriate in certain situations.

[0116] A structural array, such as designated by reference numerals420A-420C, configured and operative to maintain a plurality of samplesas set forth in more detail below, may be supported at each sample sitemember 414,415. It is noted that the depiction of structural arrays420A-420C is representative only, and that certain physical componentsof structural arrays 420A-420C have been omitted from FIG. 4A forclarity; the particular characterization is not intended to beinterpreted in any limiting sense.

[0117] As in the illustrated embodiment, sample carrier 410 may beconstructed such that each structural array 420A-420C is supported in apredetermined spatial relationship relative to other structural arraysand relative to a respective specimen or sample container. By way ofexample, structural array 420A may be supported in a position to engagea respective well 431A in a multi-well plate 430, while structural array420B may be supported to engage a different respective well 431B inmulti-well plate 430.

[0118] In the exemplary embodiment depicted in FIG. 4A, each structuralarray in a given row of sample sites on sample carrier 410, e.g. row416, may be supported in a predetermined spatial relationship relativeto a respective specimen or sample container in a corresponding row ofwells in multi-well plate 430, i.e. row 436 in this example. Similarlyeach structural array in row 417 (e.g. structural array 420C) may besupported to engage a respective well in row 437 of multi-well plate430.

[0119] Sample carrier 410 may additionally include longitudinal frameelements 418A,418B which may support transverse members 412. In someembodiments, longitudinal elements 418A,418B may be constructed andoperative to support a label, tag, decal, or other identifying indicia419 which may be unique to sample carrier 410. As is generally known inthe art, identifying indicia 419 may incorporate a bar code, a serialnumber, or other alpha-numeric or symbolic representation, for example,and may distinguish sample carrier 410 from other sample carriersmaintained in an archive facility such as illustrated and describedabove with reference to FIG. 3.

[0120] Structural elements of sample carrier 410 may be constructed ofany material with sufficient rigidity to support structural arrays420A-420C in a desired predetermined spatial relationship, which may beinfluenced, for example, by the configuration or arrangement ofrespective sample containers such as an array of test tubes or the wellsof a multi-well plate. Additionally, longitudinal elements 418A,418B maybe constructed and dimensioned to enable manipulation and transport ofsample carrier 410 by robotics or other automated mechanisms;consequently, longitudinal elements 418A,418B may be constructed ofappropriate material to withstand forces exerted by handling or grippingmechanisms. Accordingly, the structural elements of sample carrier 410may be fabricated of polystyrene or various plastics, for example, andmay provide suitable stiffness without rendering sample carrier 410unnecessarily heavy or cumbersome.

[0121]FIG. 4B is a simplified partial longitudinal cross section, andFIG. 4C is a simplified partial transverse cross section, of a samplecarrier constructed to engage a multi-well plate. The cross sectionalview depicted in FIG. 4B is taken along longitudinal axis 499 in FIG.4A, whereas the cross sectional view depicted in FIG. 4C is taken alongthe row 416/436 in FIG. 4A. As indicated in FIGS. 4B and 4C, transversemember 412 may support sample site positioning members 413 such thateach sample site member 414,415 (and consequently, its associatedstructural array 420A-420C) is accurately positioned relative to arespective specimen or sample container (wells 431A-431C) in amulti-well plate 430. As with the illustration in FIG. 4A, structuralarrays 420A-420C are depicted in representative form for clarity.

[0122] In some embodiments, multi-well plate 430 may include one or moretransverse depressions 432; referring back to FIG. 4A, it will beappreciated that depression 432 may be oriented orthogonal tolongitudinal axis 499 and disposed intermediate rows 436,437 of wells431. Depression 432 may be dimensioned to allow acceptance of transversemember 412 when sample carrier 410 is brought sufficiently close tomulti-well plate 430. Similarly, multi-well plate 430 may include one ormore longitudinal depressions 433 (FIG. 4B) dimensioned to receivesample site positioning members 413 when sample carrier 410 is broughtsufficiently close to multi-well plate 430.

[0123] Specimen containers such as wells 431A-431C may contain specimenmaterial to be transferred to structural arrays 420A-420C. Afterappropriate alignment, which may be facilitated by automated mechanismsor robotics, for example, or conducted manually, sample carrier 410 andmulti-well plate 430 may be brought into close proximity such thattransverse member 412 enters depression 432, sample site positioningmember 413 enters depression 433, and structural arrays 420A-420Ccontact respective specimens contained in wells 431A-431C. In theforegoing manner, specimen material may be transferred to discretesample nodes (described below with reference to FIGS. 5A-5E) atstructural arrays 420A-420C.

[0124] Wells such as 431A-431C in various multi-well plates known in theart may be particularly suited to accommodate specimen material inliquid form; it will be appreciated, however, that wells 431A-431C mayalso carry specimen material in solid or even gaseous form. As notedabove, specimens may be biological or non-biological, for example.Biological specimen material may include biopolymers such as proteins orother polynucleotides, e.g. DNA. Examples of non-biological specimensmay include chlorofluorocarbons or other environmental or atmosphericpollutants.

[0125] Following transfer of sample material to structural arrays420A-420C, sample carrier 410 may be engaged with a clean, or previouslyunused, multi-well plate 430 for sample storage and preservation. Inthis embodiment, sample containers such as wells 431A-431C of multi-wellplate 430 may not contain any specimens or other material, and mayprotect samples maintained at structural arrays 420A-420C fromcontamination introduced by external sources or by contact with otheritems. Since depression 432 is configured to accommodate transversemember 412 and depression 433 is configured to accommodate sample sitepositioning member 413, the combination of sample carrier 410 andmulti-well plate 430 may accept a cover (not shown) as is generallyknown in the art of preserving samples in multi-well plates.

[0126] Longitudinal elements 418A,418B may extend beyond thelongitudinal sides 432A,432B of multi-well plate 430 and the sides ofany cover or lid. A gripping or handling apparatus oriented for usealong longitudinal axis 499 may engage longitudinal elements 418A,418Band remove sample carrier 410 (and any lid disposed thereon) frommulti-well plate 430; on the other hand, a gripping or handlingapparatus oriented for use along the transverse axis may engagetransverse sides 433A,433B of multi-well plate 430, and consequently,the entire assembly of multi-well plate 430, sample carrier 410, andcover. In the foregoing embodiment, a standard plate cover may bemodified to allow protrusion of transverse members 412 and longitudinalelements 418A,418B.

[0127]FIG. 5A is a simplified diagrammatic plan view illustrating oneembodiment of a structural array employed by a sample carrier.Structural array 520A generally corresponds to those represented anddescribed above with reference to FIGS. 4A-4C. The arrangement andoverall configuration of structural array 520A is provided by way ofexample only. In some embodiments, structural array 520A may befabricated of the same material, such as polystyrene or other polymer,for example, as the sample carrier to which it is attached.

[0128] Structural array 520A generally comprises a plurality of samplestructures such as designated by reference numerals 522 and 524. Samplestructures 522,524 may be maintained in a predetermined spatialrelationship by radial elements 521 or other suitable structuralcomponents. In the exemplary embodiment, a sample node (represented bythe small circles in FIG. 5A, one of which is designated by referencenumeral 529) may be removably attached to structural array 520A at arespective one of the sample structures 522,524; i.e. each samplestructure 522,524 may be operative to support a discrete sample node529. In turn, each sample node 529 may be operative to carry a discretesample, such as biological or non-biological sample material, forexample. Such samples may include, for example, proteins orpolynucleotides.

[0129] Sample nodes 529 may be removably attached to sample structures522,524 at attachment points 523,525, respectively. In some embodiments,attachment points 523,525 may be free from specimen material or othercontaminants such that selective removal of sample nodes 529, even bymechanical means requiring physical contact with attachment points523,525, does not introduce cross contamination risks generated byforeign material, residue from previous removal operations, or otherparticulate matter.

[0130] It will be appreciated that sample nodes 529 need not becircular, nor of uniform size, as represented in FIG. 5A, but may beformed in any of numerous other shapes and sizes. FIG. 5B is asimplified illustration of various embodiments of a sample node. Thoseof skill in the art will appreciate that several polygons, polyhedrons,and spherical or oblong shapes are contemplated and may be selectedbased upon various factors such as the desired node size and density,the saturation limit of the material used for nodes 529, the accuracyand precision of the device used to remove nodes 529 as described below,and the like. The present disclosure is not intended to be limited bythe shape, size, or dimensional characteristics of sample nodes 529.

[0131] A sample node 529 such as illustrated and described may generallycomprise, or be constructed entirely of, a sample support medium; insome embodiments, for example, sample node 529 may simply be coated witha selected sample support medium. In accordance with one aspect of thepresent invention, sample support media for use at sample nodes 529 maybe embodied in paper or cellulose, polystyrene, plastic, or othersuitable support material constructed and operative to serve as along-term storage mechanism for biological or other samples in adesiccated form. Specimen material in solid, liquid, or gaseous form maybe brought into contact with the sample support medium and stored assamples at discrete sample nodes 529.

[0132] In some embodiments, for example, such a sample support mediummay maintain desiccated samples of biopolymers, including DNA andproteins, or non-biological samples, including fluorocarbons orchlorofluorocarbons (CFCs) and synthetic chemical compounds. As notedabove, filter paper substrate embodiments are currently known in theart; the present disclosure is not to be construed as so limited,however. A support medium suitable for implementation at sample nodes529 may generally comprise any appropriate material known in the art ordeveloped and operative in accordance with known principles, and may beselected in accordance with binding properties as a function of the typeof sample to be carried and maintained.

[0133] In that regard, an appropriate sample support medium may be solidor porous, for example, depending, in part, upon the type of specimen tobe stored as samples at discrete sample nodes 529. Additionally oralternatively, sample support medium may be treated with one or morechemical compounds or derivatized, for instance, to manipulate variousbinding properties prior to contact with a specimen. Positive ornegative electrical charges, chemical compositions, bindingcharacteristics, antibodies, lectins, porosity, and other operationalfactors for sample nodes 529 may be selected in accordance with the typeof sample support medium implemented and the type or nature of anyprocesses performed thereon.

[0134] Biological and non-biological samples may be stored in acontrolled environment. In that regard, humidity, temperature, and otherenvironmental factors may be controlled in a fireproof vault or otherstructure employed as an archive as set forth above. In someembodiments, environmental conditions may be selectively altereddepending, for instance, upon the nature of the samples, the compositionof the sample support medium employed at sample nodes 529, or both, topreserve longevity of the samples for decades. In a DNA archivalembodiment, for example, the sample support medium may include achemically treated surface or structure, serving to lyse particularspecimen cells and to immobilize the DNA structure to the sample supportmedium or substrate at discrete sample nodes 529. Additionally oralternatively, preservatives may be applied, embedded, impregnated, orotherwise incorporated onto or into the sample support medium; suchpreservatives may ensure the stability and fidelity of the DNA structurefor tens of years. Sample nodes 529, which may be characterized bydiscrete pellets or spheres as represented in FIGS. 5A and 5B, may beautomatically removed from a sample carrier and selectively deposited inparticular wells disposed in multi-well plates; samples deposited inparticular wells may, in turn, be selected for subsequent processing(e.g. such as with polymerase chain reaction (PCR) assays, and thelike).

[0135] Cross contamination is virtually eliminated by storing thesamples on discrete sample nodes 529. In some instances, sample nodes529 may be optically separated from the sample carrier, thereby avoidingany mechanical contact involving a mechanical sample removal deviceduring retrieval, extraction, purification, packaging, and shipping.Moreover, since a sample carrier such as illustrated in FIGS. 4A-4C maybe amenable to manipulation by standard robotics, an entire archivefacility may be easily automated to achieve high I/O rates (for example,greater than one hundred samples per day).

[0136] DNA which is archived and retrieved as set forth above withreference to FIGS. 3-5B may be well suited for large-scale geneticanalysis, and may yield samples which are superior (relative toconventional liquid phase or cryogenic technologies) forpharmacogenetics or other types of genetic discovery analysis.Specifically, implementation of discrete sample nodes 529 mayautomatically standardize the quantity and quality of DNA storage due tothe inherent loading properties of the sample support medium and anyembedded chemicals serving to diminish PCR inhibitors; accordingly, therequirements and complexities of quantification procedures followingpurification in conventional DNA extraction may be simplified, reduced,or eliminated entirely. Additionally, desiccated archive samples are notcontinuously degraded during repeated freezing and thawing cycles as iscommon in cryogenic systems.

[0137]FIG. 5C is a simplified block diagram illustrating one embodimentof a system and method of removing a sample node from a sample carrierstructural array. As indicated, a removed sample node 529 may bedeposited in a sample container such as a well 531 in a standard ormodified multi-well plate (FIGS. 4A-4C); the remainder of the samplecarrier to which structural array 520C is attached and the remainder ofthe multi-well plate have been omitted from FIG. 5C for clarity.

[0138] Structural array 520C may be supported from a sample carrier by asample site positioning member 513 and a sample site member 514. As setforth in detail above, a discrete sample node 529 may be attached tosample structure 524 at attachment point 525. In the FIG. 5C embodiment,a laser 599 may provide sufficient energy in the form of coherent lightto attachment point 525 to remove sample node 529. Those of skill in theart will appreciate that other means, mechanisms, or devices may beemployed to remove sample node 529 from structural array 520C;accordingly, a cutting or clipping apparatus, micro-electromechanicaldevices (MEMS), or electrical circuit elements such as fuses, forexample, may be employed in lieu of laser 599 to provide energynecessary to separate sample node 529 from sample structure 524.

[0139] As discrete sample nodes 529 are removed from structural array520C during the useful life of a given sample carrier, fewer samplestructures 522,524 may be supporting a sample node 529, i.e. fewersample nodes 529 remain. Accordingly, the laser in the exemplary FIG. 5Cembodiment may be enabled to identify or otherwise to ascertain thelocation of a particular sample node 529 targeted for removal. In thatregard, each sample structure 522,524 and its respective attachmentpoint 523,525 may be addressed and catalogued, for example.

[0140] Addressing or location information may be stored in a datastorage medium as described above with reference to FIG. 3, and mayenable laser 599 or other sample node removal means to identify and totarget a specific attachment point 523,525 supporting a discrete samplenode 529 on structural array 520C. Where the particular structuralarrangement or configuration of structural array 520C is known andsample node addressing information is stored as one or more datarecords, computerized robotic systems or computer-targeted laser 599 maybe controlled precisely to remove a selected sample node 529; similarly,the system may be apprised, through updated data records, of samplenodes which have been removed such that a detailed search of the entirestructural array 520C may not be required for subsequent sample noderemoval operations.

[0141] Additionally or alternatively, laser 599 or another sampleremoval device, such as a robotic clipping mechanism, for example, maybe equipped with machine vision or other optical sensors. In thisembodiment, a sample locator device may gather optical information whichmay subsequently be used to guide a sample node removal apparatus suchas laser 599 in an interactive manner, ie. the system may methodicallyexamine each sample structure 522,524 in a predetermined order, forexample, or under control of an operator, until a sample structure522,524 supporting a sample node 529 is detected. This embodiment may beimplemented in situations where the configuration or orientation of allthe components of structural array 520C is not known or has changed(e.g. due to breakage or structural failure), or where the history ofsample node removal operations for a given structural array 520C is notknown; in such situations, a detailed “map” or other indication ofremaining sample node locations may not be available.

[0142]FIG. 5D is a simplified block diagram illustrating anotherembodiment of a system and method of removing a sample node from asample carrier structural array. As in the FIG. 5C embodiment, a removedsample node 529 may be deposited in a sample container 531 such as awell in a standard or modified multi-well plate, a test tube, or othervessel. The omission of a sample structure positioning member from FIG.5D is representative of the fact that a given sample carrier may supportonly a single structural array 520D.

[0143] In this embodiment, structural array 520D may be supported simplyby a sample site member 514, which may include an identificationstructure 518 bearing a label or other identifying indicia 519 such as abar code, serial number, and the like, substantially as described above.

[0144] A sample removal device 599 may be employed to remove sample node529 from structural array 520D; accordingly, sample removal device 599may generally comprise an optical component 598, a positioning component597, and a clipping component 596.

[0145] Optical component 598 may generally comprise machine visiontechnology, video cameras, or other optical sensors which are capable ofidentifying or locating the elements of structural array 520D usinginstruments or receptors which are sensitive to various portions of theelectromagnetic spectrum. In this embodiment, optical information (fromthe visible portion of the spectrum) or other electromagneticinformation (such as microwave or infrared frequencies, for example) maybe used to ascertain the configuration and arrangement of structuralarray 520D. The foregoing information may be used to automate theremaining components of sample removal device 599, for example; acompletely automated robotic system may be developed around thefunctionality of optical component 598. Alternatively, output fromoptical component 598 may be transmitted or otherwise displayed invisual form for a system operator, who may control other elements ofsample removal device 599 in accordance with optical informationregarding structural array 520D obtained and provided by opticalcomponent 598.

[0146] Whether automated or operator-controlled, positioning component597 may be employed to guide clipping component 596 to an appropriateposition relative to structural array 520D to remove a targeted samplenode 529. In that regard, positioning component 597 may include some orall of the following: servos; motors; hydraulic or electromechanicalarms, appendages, or conveyors; gyroscopes; rotating shafts; pistons;gears; guide rails; support beams; and other elements generally known inthe art for translating and articulating apparatus in three dimensions.

[0147] As set forth above, positioning component 597 may be operative tomove clipping component 596 or another sample node removal apparatus.Additionally or alternatively, positioning component 597 may beconstructed and operative to move structural array 520D or the samplecarrier to which it is attached. For example, structural array 520D orthe sample carrier may be mounted on a movable stage which translates inone or two dimensions. Whether positioning component 597 moves clippingcomponent 596, structural array 520D, or both, it will be appreciatedthat such a mechanical positioning system may bring a sample noderemoval device into a desired position relative to structural array520D, i.e. enabling removal of a targeted sample node 529.

[0148] As noted above with reference to FIG. 5C, various devices such aslasers, micro-electromechanical devices (MEMS), or electrical circuitelements may be employed to remove a targeted sample node 529 from astructural array. The exemplary FIG. 5D embodiment of clipping component596 comprises a mechanical clipper 595 which may be operative to seversample structure 524 at attachment point 525. It will be appreciatedthat use of a mechanical device such as clipper 595 may require physicalcontact with sample structure 524 during normal operation; to avoid riskof cross contamination from one sample removal operation to the next, itmay be desirable to ensure that sample structure 524 is free of specimenmaterial or other possible contaminants at the point at which clipper595 makes contact.

[0149]FIG. 5E is a simplified block diagram illustrating one embodimentof a sample node identification or location system. To maximize thedensity of samples maintained in an archive facility such as illustratedin FIGS. 1-3, biomolecules (such as DNA and proteins, for example) ornon-biological samples to be archived may be tagged electronically forsubsequent identification. Recently, micro-transceiver systems have beendeveloped by researchers and proposed for use in active drug deliverytechniques. As illustrated in FIG. 5E, for example, an electronicmicro-transceiver 590A, may be integrated into a discrete sample node529; additionally or alternatively, a transceiver 590B may be attachedto, or integrated into, sample structure 524 proximal to attachmentpoint 525.

[0150] As set forth above, biomolecules or other sample material may beattached on the surface (or may penetrate into the sample supportmedium) of sample node 529 for high density archiving. Amicro-transceiver 590A,590B may transmit omni-directional RF signals,for example, enabling a receiver at a robotic system to identify and tolocate sample node 529 using associated signature signal frequencies,transmission patterns, or other information. In this embodiment, aunique signal transmitted by transceiver 590A,590B may be received bythe positioning component 597 in FIG. 5D and used to direct thepositioning of robotic instrumentation or sample removal component 596.

[0151] Additionally or alternatively, a remote control system maintainedat an archive facility may transmit signals to transceivers 590A and590B to initiate operation of MEMS, for example, or to activatemicrocircuits or circuit elements operative to remove sample node 529from sample structure 524. In the foregoing manner, sample node removalmay be triggered electronically based upon signals transmitted totransceivers 590A and 590B.

[0152] As described above, it may be desirable to ensure that samplestructure 524 is free of specimen material or other possiblecontaminants to avoid risk of cross contamination. The FIG. 5Eembodiment illustrates a region 594 representing the point at which amechanical clipping device may make contact with sample structure 524.As set forth in more detail below, after specimen material istransferred to sample node 529, sample structure 524 or the entirestructural array or sample carrier, for instance, may be washed orcleaned to remove contaminants or specimen residue from region 594 orthe entirety of sample structure 524.

[0153]FIG. 6 is a simplified flow diagram illustrating one embodiment ofa method of preparing an archive sample for analysis. An archive sampleto be analyzed may be identified or selected at block 601. For example,a researcher may browse a list or catalogue of available samples (e.gmaintained at an archive facility as described above with reference toFIGS. 1-3); the list of archive samples may additionally becross-referenced with data records containing information related tosample sources as set forth in detail above, for example. In this sense,identifying or selecting the sample to be analyzed may simply representa process of designating or otherwise indicating a sample or type ofsample which may be appropriate for the intended analytical procedure.

[0154] Upon identification of a suitable sample or sample type, a samplecarrier which supports one or more appropriate sample nodes (i.e. asample node carrying the selected sample) may be identified and locatedas indicated at block 602. As with identification of a sample at block601, locating a sample carrier at block 602 may be executed manually,for example, by a researcher or a technician; alternatively,identification of a sample and location of a sample carrier may beautomated, for example with bar code readers and robotic sample carrierretrieval apparatus, as described above with reference to FIGS. 3 and 5.

[0155] At blocks 603 and 604, a structural array and a sample node maybe identified and located as set forth above with reference to FIGS.5C-5E. Accurate address or location information may be maintained in adata storage medium such that location of a structural array and aparticular sample node may be accomplished without the use of opticalsystems or machine vision techniques. In some embodiments, however, itmay be desirable to identify and to locate a discrete sample nodeactively, for example, with the assistance of optical sensors or videosignal information.

[0156] Removal of one or more identified sample nodes at block 605 mayrequire implementation of a sample node removal device or means forseparating the sample node from its respective sample structure. As setforth above, suitable devices or apparatus include, but are not limitedto, the following: targeted lasers; automated or manually controlledclipping, cutting, slicing, or breaking tools; programmable MEMS, whichmay be small enough and sufficiently agile to maneuver on the componentsof the structural array illustrated in FIGS. 5A-5E; electrical fuseswhich, when blown, may create sufficient heat to destroy the attachmentpoint thereby to separate a sample node from its respective samplestructure; or any other mechanisms configured and operative to deliverenough energy to the sample structure to remove the sample node.

[0157] As described above, each structural array, and consequently itssample nodes, may be positioned and dimensioned in a predeterminedspatial relationship, particularly with respect to one or more samplecontainers. A sample node removed from a structural array (block 605),may be deposited in a sample container such as a well in a multi-wellplate, a test tube or other experimental or storage vessel, a paper orcardboard bindle, a shipping container, and the like.

[0158] As indicated at block 606, a removed sample node may be preparedfor analysis. The preparation indicated in the FIG. 6 embodiment mayrepresent any or all of the following, inter alia: addition of reagentsor other chemicals to a sample container; purification of the sampleremoved from the sample carrier; washing, packaging, and shipping orother transportation to a remote site for analysis; and so forth.

[0159]FIG. 7 is a simplified flow diagram illustrating one embodiment ofa sample archival method. As indicated at block 701, the storage orarchival process may generally begin with acquiring consent from apatient or other specimen source. Much like the conventional archivingprocess, informed consent may be obtained by a professional recruiterafter explaining the nature of the research to be conducted at anarchive facility and any techniques or technologies employed by thearchive facility to ensure specimen source confidentiality. It will beappreciated that, in the case of non-biological specimens, for example,acquiring informed consent at block 701 may be neither possible nornecessary.

[0160] Information concerning or relating to the specimen source may beobtained as indicated at block 702. By way of example, a questionnaireor other form may be completed by the specimen source (e.g. a patient ora patient's guardian or representative) with the aid of a trainedprofessional; the questionnaire or form may be electronic, promptingcomputer input responses. Additionally or alternatively, some or all ofthe information obtained from the specimen source may be oral or handwritten; in this exemplary embodiment, a technician or data entryprofessional may input relevant information into a computer forrecordation in a database. A standardized or modified computerspreadsheet or other proprietary application software which iscompatible with the database may be used for data recordation. In someembodiments, data transcription errors may be minimized and maximumefficiency may be achieved where source- and specimen-specificinformation is input directly into a computerized system.

[0161] As depicted at block 703, a unique code, serial number, or otheridentifier may be assigned to the information associated with thespecimen and its source. As illustrated and described in detail abovewith reference to the sample carriers of FIGS. 4A and 5D, a respectivebar code or other identifying indicia may be used to identify specificsamples. In the case of specimens and source-specific information, suchan identifier may be assigned early in the archival process, possiblyeven before the specimen is obtained, as in the FIG. 7 embodiment.Identification of a specimen source and accurate association andcross-referencing with, for instance, the medical history of the sourceor other relevant information, may facilitate efficiency and properinterpretation of results in large-scale DNA or genomic studies, forexample.

[0162] Data specific to the specimen and the source may be recorded asdata records in a database as indicated at block 704. As is generallyknown in the art, data records may be accessed or retrieved inaccordance with the unique identifier associated therewith and assignedas set forth above. As illustrated and described in detail above withreference to FIG. 3, data storage media serving as central informationrepositories may be maintained at various locations in an archivefacility. Data may be transmitted to an archive facility, for example,via a network connection such as described above; in that regard, asecure internet connection employing Secure Sockets Layer (SSL)encryption technology (128-bit encryption) or a VPN connection (168 bitencryption) may ensure data integrity and confidentiality of sensitiveinformation. Information associated with each contributing specimensource and transmitted to the archive facility may be formatted inaccordance with database requirements, for example, and subsequentlymade available to archive facility clients via the network connection;in some embodiments, database formats and access authorizations may beselected to preserve specimen source confidentiality.

[0163] A specimen may be obtained from the source and associated withthe correct unique identifier as indicated at block 705. For example,blood may be drawn from a patient by a member of a pathology nursingstaff. A portion of a standard blood draw (e.g. approximately 1-5 ml ofa total 10 ml draw) may be used to create samples for use in conjunctionwith a sample carrier as described in detail above with reference toFIGS. 4 and 5.

[0164] In accordance with this embodiment, a sample carrier maygenerally support one or more structural arrays, each comprising aplurality of discrete sample nodes. As set forth above, each sample nodemay be operative to carry a sample on a sample support medium. Some ofthe blood drawn may be deposited in a specimen container, for example, atest tube or one or more wells in a multi-well plate. The structuralarrays of the sample carrier may selectively be placed in proximity tothe respective specimen containers such that the plurality of samplenodes are selectively exposed to respective specimens. The samplesupport medium at the sample nodes may absorb, lyse, or otherwise bindthe blood spotted in the respective specimen containers. In theforegoing exemplary manner, specimen material may be transferred todiscrete sample nodes as represented at block 706. In some embodiments,preservatives may be applied or the sample nodes may be allowed to drysuch that each sample is maintained in desiccated form.

[0165] Sample nodes or entire sample carriers may be washed or rinsed,for example with detergents or other chemicals, to remove specimenresidue or other contaminants from sample structures as described above.The cleaning process, represented at block 707, may reduce the risk ofcross contamination potentially introduced by operation of the sampleremoval device.

[0166] As noted above with reference to FIGS. 4A and 5D, sample carriersmay be bar-coded, labeled, tagged, or otherwise provided with uniqueidentifying indicia, decipherable by an optical scanner or machinevision technology, which may facilitate automated or manual sample andsample carrier tracking. A bar code or other identification on aparticular sample carrier may provide information related to the sourceof the specimen used for each structural array on the sample carrier;further, the identifying indicia may also provide information related tothe structural arrangement or configuration of each structural array,i.e. the number of discrete sample nodes in a particular structuralarray, information concerning the spatial orientation of each discretesample node, and so forth. The location of each sample within the samplecarrier may be recorded as indicated at block 708; this recordation maybe coordinated with production of the bar code or other indicia for thesample carrier.

[0167] Covered storage carriers may be shipped to an archive facilityfrom remote locations, i.e. wherever specimens are obtained, typicallyby express mail. Since shipping blood or other biological samples in adesiccated or dry state does not require treatment as a hazardousmaterial, sample carriers supporting desiccated samples may beconveniently shipped anywhere in the world.

[0168] At an archive facility such as described above with reference toFIG. 3, robotics or automated mechanical systems may be used to placesample carriers in receptacles (block 709). Receptacles may be embodiedin shelves, drawers, racks, or other structures constructed to receivesample carriers; accordingly, the form and particular structuralconfiguration of receptacles at an archive facility may generally be afunction of the type and configuration of the sample carriers to bestored.

[0169] In one embodiment, an automated shelf or receptacle for storageand retrieval may be constructed to accommodate a sample carrier engagedwith a multi-well plate as described above with reference to FIG. 4A. Inthis embodiment, longitudinal frame elements of the sample carrier mayextend beyond the multi-well plate. A robotic gripping mechanism maygrasp the entire assembly (i.e. the sample carrier and the multi-wellplate), or only the sample carrier, depending upon the orientation ofthe gripping mechanism relative to the receptacle.

[0170] It will be appreciated that various alternatives exist withrespect to the FIG. 7 embodiment, and that the presented order of theindividual blocks is not intended to imply a specific sequence ofoperations to the exclusion of other possibilities; the particularapplication and overall system requirements may dictate the mostefficient or desirable sequence of the operations set forth in FIG. 7.For example, specimen acquisition and association with an identifier(represented at block 705) may precede block 704, or may even occurprior to obtaining source-specific information at block 702, providedthat appropriate provisions are made for assigning a unique identifier.Similarly, recordation of the location of samples at block 708 mayprecede, or occur simultaneously with, transfer of specimen material todiscrete sample nodes at block 706 in certain situations.

[0171]FIG. 8 is a simplified flow diagram illustrating one embodiment ofa method of retrieving and preparing an archive sample for analysis. Asindicated at block 801, the archive sample retrieval process in anexemplary embodiment may generally begin with receipt of a request. Amedical researcher or technician, for instance, may request retrieval ofblood or DNA samples. Such requests may be transmitted from remotenetwork clients across a communication network. In situations where aresearcher is interested in a specific disease or a specific type ofanalysis, the request may be related to, or include relevant informationwith respect to, a particular type of experiment or analysis, forexample.

[0172] In an embodiment such as depicted and described above withreference to FIGS. 1-3, for example, a researcher at a remote networkclient location may transmit a request to an archive facility via anetwork. Remote inquiries may seek to ascertain the availability ofsamples which may be appropriate for the intended experimentation, andmay include requests for access to data records or other clinicalinformation related to samples and sample sources; as noted above, suchdata records may be maintained in one or more data structures at thearchive facility. Through Boolean search queries, for example, or otherdata searching techniques which are generally known in the art, one ormore suitable samples may be identified responsive to the request;suitability of particular samples may be based upon relevant clinicaldata and history. Sample identification is generally depicted at block802, and may be facilitated by random sample selection from designatedor specified sample categories or sample types. Accordingly, broadcategories containing many samples, all of which satisfy selectedcriteria, may be narrowed automatically through random selection ofparticular samples within the defined categories.

[0173] In some embodiments, a purchase order specifying some or all ofthe identified samples may be submitted, followed by a request that thesamples be prepared for shipment to a remote location; additionally oralternatively, a researcher may request that certain analyses,experiments, or portions thereof be performed using the identifiedsamples at the archive facility. In any event, a sample carriersupporting the identified sample may be located in the archive facility(block 803). As described in detail above, location and retrieval ofparticular sample carriers may be facilitated by unique identifyingindicia disposed on each sample carrier in the archive facility;robotics and machine vision or bar code reader technology may enableautomatic location and retrieval of sample carriers. Alternatively, atechnician or administrator at the archive facility may locate andretrieve one or more sample carriers at block 803 manually.

[0174] As indicated at block 804, preparation of a sample for analysismay involve detecting a location of a discrete sample node on theretrieved sample carrier; as set forth above with reference to thesample carriers illustrated in FIGS. 4 and 5, structural arrays andsample structures may support a plurality of discrete sample nodes in apredetermined spatial relationship relative to each other and relativeto a sample container such as a test tube or a particular well of amulti-well plate. As sample nodes are removed from a particular samplecarrier during its useful life, the efficient detection of samplestructures to which sample nodes are still attached may increase overallsystem throughput. As noted above, detecting the location of a samplenode on a sample carrier may be facilitated by, inter alia, data recordsrelated to previous sample removal operations, machine vision or opticaltechnology, or operator-assisted positioning tools for robotic sampleremoval mechanisms.

[0175] Following detection or location, discrete sample nodes may beremoved from the sample carrier as indicated at block 805. Removal ofsample nodes may be performed with optical equipment as illustrated inFIG. 5C; as described above, the FIG. 5C embodiment may virtuallyeliminate risks of cross contamination due to material transferred fromone sample node to the next by a mechanical sample removal tool ordevice. Specifically, the FIG. 5C embodiment may employ a laser coupledto a precise positioning system; lased, coherent light may sever thesample structure supporting the sample node, depositing the sample nodeinto a sample container for future processing.

[0176] Alternatively, the mechanical clipper (FIG. 5D) or equivalentcutting devices may be employed for sample removal at block 805; in anembodiment utilizing a mechanical sample node removal tool, the tool maybe constructed and operative to make contact only with the samplestructure supporting the sample node to be removed. Accordingly, crosscontamination between samples may be avoided, since the sample noderemoval device does not make contact with any sample material.

[0177] At decision block 806, a determination may be made with respectto shipping the samples. Where a request for shipment has been made bythe researcher, for example, the sample container into which the samplenode has been deposited may be sealed and packaged for shipment; asindicated at block 807, samples may be purified with one or moreappropriate procedures prior to shipment such that, upon arrival at aremote location, the samples may be in condition for immediateexperimentation (block 899). By way of specific example, a PCRamplification may precede shipment; the DNA attached to the samplesupport medium at the sample node may serve as the DNA template, and PCRreagents may then be deposited directly into the sample container.

[0178] Where shipping has not been requested, or where analysis isrequested prior to shipment, processing may proceed in accordance withthe request as indicated at block 808. Various testing, experimentation,and analysis may be conducted at the archive facility or at a remotefacility as set forth in detail above. Test results, data, or otherrelevant information may be recorded as indicated at block 809;additionally or alternatively, the acquired data may be transmitted,either responsive to a specific request or automatically, for example,to a researcher at a remote location via a network connection asdescribed above with reference to FIGS. 1-3.

[0179] Those of skill in the art will appreciate that the FIG. 8embodiment is provided by way of example only, and that variousalternatives exist. In an embodiment accommodating both processing at anarchive facility as well as shipment of samples to a remote site, forexample, the operations indicated at blocks 807 and 899 may followrecordation and transmission of experimental results at block 809. Asanother alternative, the determination at decision block 806 maydirectly follow reception of a request (block 801) or sampleidentification (block 802); it is possible in this embodiment, forexample, that an entire sample carrier may simply be shipped directly toa remote location without sample node detection, removal, or analysis.

[0180] In addition to sample archival and retrieval, myriad DNA analysisservices may be provided to remote clients in conjunction withaffiliated genomics companies. For example, researchers may be primarilyinterested in the genotypes of specific patient or sample classes asopposed to the samples themselves. In this situation, remote clients mayspecify not only specific samples or sample categories of interest, butalso particular genes or gene sequences of interest. An affiliatedcompany, for example, under contract with the archive facility, maydesign a custom DNA chip used to genotype the selected samples;accordingly, genotyping results may be transmitted electronically (via asecure or encrypted network connection, for example) to a remote client.Since the sample nodes may be delivered in standard microtiter plates asset forth above, samples may be delivered in suitable condition forimmediate amplification for subsequent desired experimentation oranalysis.

[0181] The embodiments described above are scalable; as numerous archivefacilities are employed and networked, a vast database of samples andinformation related to sample sources may be statistically mined toreveal DNA-directed therapeutics and, ultimately, cures for many geneticailments.

[0182] The present invention has been illustrated and described indetail with reference to particular embodiments by way of example only,and not by way of limitation. Those of skill in the art will appreciatethat various modifications to the disclosed embodiments are within thescope and contemplation of the invention. Therefore, it is intended thatthe invention be considered as limited only by the scope of the appendedclaims.

What is claimed is:
 1. A sample archive system comprising: a pluralityof sample carriers configured to support a plurality of sample nodes ina predetermined spatial relationship; sample storage means forselectively placing said plurality of sample carriers in an archive; andsample node removal means for locating and removing selected ones ofsaid plurality of sample nodes.
 2. The system of claim 1 wherein saidsample node removal means comprises a laser.
 3. The system of claim 1wherein said sample node removal means comprises a mechanical clippingtool.
 4. The system of claim 1 further comprising an optical componentoperative to detect the location of said selected ones of said pluralityof sample nodes.
 5. The system of claim 4 further comprising apositioning component operative to position said sample node removalmeans responsive to signals transmitted by said optical component.
 6. Asample archive system comprising: a plurality of sample carrierreceptacles; each of said plurality of sample carrier receptaclesconfigured to receive one or more sample carriers supporting a pluralityof sample nodes; a sample carrier storage device operative to placeselected ones of said one or more sample carriers in selected ones ofsaid plurality of sample carrier receptacles; a sample carrier locationdevice operative to locate said selected ones of said one or more samplecarriers; a sample carrier retrieval device operative to retrieve saidselected ones of said one or more sample carriers from ones of saidplurality of sample carrier receptacles; and sample node removal meansfor identifying and removing selected ones of said plurality of samplenodes.
 7. The system of claim 6 wherein at least a portion of saidplurality of sample carrier receptacles includes a rack.
 8. The systemof claim 6 wherein at least a portion of said plurality of samplecarrier receptacles includes a drawer.
 9. The system of claim 6 whereinsaid sample carrier location device is a bar code reader.
 10. The systemof claim 6 wherein said sample node removal means comprises a laser. 11.The system of claim 6 wherein said sample node removal means comprises amechanical clipping tool.
 12. The system of claim 10 wherein said samplenode removal means further comprises an optical component operative todetect the location of said selected ones of said plurality of samplenodes.
 13. The system of claim 12 wherein said sample node removal meansfurther comprises a positioning component operative to position saidlaser responsive to signals transmitted by said optical component. 14.The system of claim 6 further comprising means for processing a samplesupported by said selected ones of said plurality of sample nodes. 15.The system of claim 6 further comprising a controller for controllingoperation of said sample carrier storage device and said sample carrierretrieval device.
 16. A sample archive system comprising: an archivecomprising a plurality of sample carrier receptacles; each of saidplurality of sample carrier receptacles configured to receive one ormore sample carriers supporting a plurality of sample nodes; and arobotics system comprising mechanisms operative to store and to retrieveselected ones of said one or more sample carriers from said archive. 17.The system of claim 16 further comprising a sample carrier locatorcoupled to said robotics system and operative to detect a location ofsaid selected ones of said one or more sample carriers.
 18. The systemof claim 17 wherein said sample carrier locator comprises an opticalsensor.
 19. The system of claim 18 wherein said robotics system isautomatically responsive to signals from said sample carrier locator.20. The system of claim 16 further comprising a sample node removaldevice operative to identify and to remove selected ones of saidplurality of sample nodes from selected ones of said one or more samplecarriers.
 21. The system of claim 20 further comprising a sample nodelocator coupled to said sample node removal device and operative todetect a location of said selected ones of said plurality of samplenodes.
 22. The system of claim 21 wherein said sample node removaldevice is automatically responsive to signals from said sample nodelocator.
 23. The system of claim 21 wherein said sample node locatorcomprises a respective transceiver incorporated in each of saidplurality of sample nodes.
 24. The system of claim 21 wherein saidsample node locator comprises an optical sensor.
 25. The system of claim16 wherein at least a portion of said plurality of sample carrierreceptacles includes a rack.
 26. The system of claim 16 wherein at leasta portion of said plurality of sample carrier receptacles includes adrawer.
 27. The system of claim 18 wherein said sample carrier locatoris a bar code reader.
 28. The system of claim 20 wherein said samplenode removal device comprises a mechanical clipping tool and amechanical positioning system to position said mechanical clipping toolrelative to said selected ones of said plurality of sample nodes. 29.The system of claim 20 wherein said sample node removal device comprisesa laser and a mechanical positioning system to position said laserrelative to said selected ones of said plurality of sample nodes. 30.The system of claim 20 further comprising means for processing a samplesupported by said selected ones of said plurality of sample nodes. 31.The system of claim 20 further comprising a computer operative tocontrol said robotics system and said sample node removal device. 32.The system of claim 24 wherein said sample node removal device comprisesa mechanical clipping tool and a mechanical positioning system toposition said mechanical clipping tool relative to said selected ones ofsaid plurality of sample nodes responsive to signals transmitted by saidoptical sensor.
 33. The system of claim 24 wherein said sample noderemoval device comprises a laser and a mechanical positioning system toposition said laser relative to said selected ones of said plurality ofsample nodes responsive to signals transmitted by said optical sensor.34. A method of archiving samples; said method comprising: selectivelytransferring a specimen to a plurality of discrete sample nodes attachedto a sample carrier; archiving said sample carrier in an archivefacility; and recording the location of said sample carrier in saidarchive facility.
 35. The method of claim 34 further comprising washingsaid plurality of discrete sample nodes subsequent to said selectivelytransferring.
 36. The method of claim 34 further comprising assigningidentifying indicia for said sample carrier in accordance with saidrecording.
 37. The method of claim 36 wherein said indicia comprises abar code.
 38. The method of claim 34 wherein said recording compriseswriting data records associated with said plurality of discrete samplenodes to a computer readable data storage medium.
 39. The method ofclaim 34 further comprising allowing said plurality of discrete samplenodes to desiccate subsequent to said selectively transferring.
 40. Themethod of claim 34 further comprising selectively applying apreservative to said plurality of discrete sample nodes subsequent tosaid selectively transferring.
 41. The method of claim 34 wherein saidspecimen is protein.
 42. The method of claim 34 wherein said specimen isa polynucleotide.
 43. The method of claim 42 wherein said polynucleotideis DNA.
 44. The method of claim 34 wherein said specimen isnon-biological.
 45. A method of archiving samples; said methodcomprising: obtaining a specimen from a source; associating anidentifier to said source and to said specimen; writing said identifierand information associated with said source and said specimen to a datastructure; selectively transferring said specimen to a plurality ofdiscrete sample nodes attached to a sample carrier; and placing saidsample carrier in a sample carrier receptacle at an archive facility.46. The method of claim 45 further comprising recording the location ofsaid sample carrier in said archive facility.
 47. The method of claim 45wherein said specimen is protein.
 48. The method of claim 45 whereinsaid specimen is a polynucleotide.
 49. The method of claim 48 whereinsaid polynucleotide is DNA.
 50. The method of claim 45 wherein saidspecimen is non-biological.
 51. The method of claim 45 furthercomprising acquiring consent to obtain said specimen.
 52. The method ofclaim 45 further comprising washing said plurality of discrete samplenodes subsequent to said selectively transferring.
 53. The method ofclaim 45 further comprising assigning identifying indicia for saidsample carrier in accordance with said associating and said selectivelytransferring.
 54. The method of claim 53 wherein said indicia comprisesa bar code.
 55. The method of claim 46 wherein said recording compriseswriting data records associated with said plurality of discrete samplenodes to a computer readable data storage medium.
 56. The method ofclaim 45 further comprising allowing said plurality of discrete samplenodes to desiccate subsequent to said selectively transferring.
 57. Themethod of claim 45 further comprising selectively applying apreservative to said plurality of discrete sample nodes subsequent tosaid selectively transferring.
 58. A computer readable medium encodedwith data and computer executable instructions; the data andinstructions causing an apparatus executing the instructions to: receiveinformation regarding a sample and a source of said sample; assign anidentifier to said sample, said source, and said information; recordsaid identifier and said information in a data structure; and record thelocation within a sample carrier of each of a plurality of discretesample nodes supporting said sample.
 59. The computer readable medium ofclaim 58 further encoded with data and computer executable instructionsand further causing an apparatus to transmit control signals to a remotedevice at an archive facility.
 60. The computer readable medium of claim58 further encoded with data and computer executable instructions andfurther causing an apparatus to transmit control signals to a samplenode removal device operative to locate and to remove selected ones ofsaid plurality of discrete sample nodes.
 61. The computer readablemedium of claim 58 further encoded with data and computer executableinstructions and further causing an apparatus to transmit controlsignals to a sample carrier storage device operative to place selectedones of a plurality of sample carriers in an archive.
 62. The computerreadable medium of claim 61 further encoded with data and computerexecutable instructions and further causing an apparatus to transmitcontrol signals to a sample carrier retrieval device operative toretrieve said selected ones of said plurality of sample carriers fromsaid archive.
 63. A method of preparing an archive sample for analysis;said method comprising: identifying a sample to be analyzed; responsiveto said identifying, ascertaining a location of said sample on adiscrete sample node supported by a sample carrier; responsive to saidascertaining, removing said discrete sample node from said samplecarrier; and preparing said sample for analysis.
 64. The method of claim63 wherein said identifying comprises interrogating a data structure.65. The method of claim 63 wherein said ascertaining comprises utilizingan optical sensor.
 66. The method of claim 63 wherein said ascertainingcomprises reading a bar code.
 67. The method of claim 63 wherein saidascertaining comprises identifying a unique signal transmitted from atransceiver attached to said discrete sample node.
 68. The method ofclaim 67 wherein said removing comprises transmitting a control signalto said transceiver.
 69. The method of claim 63 wherein said removingcomprises utilizing a laser.
 70. The method of claim 63 wherein saidremoving comprises utilizing a mechanical clipping tool.
 71. The methodof claim 63 wherein said preparing comprises depositing said discretesample node in a sample container.
 72. The method of claim 63 whereinsaid preparing comprises washing sample material attached to saiddiscrete sample node.
 73. The method of claim 63 wherein said sample isnon-biological.
 74. The method of claim 63 wherein said sample isbiological.
 75. The method of claim 74 wherein said sample is apolynucleotide.
 76. The method of claim 75 wherein said preparingcomprises amplifying said polynucleotide.
 77. A method of preparing anarchive sample for analysis; said method comprising: receiving a requestrelated to an experiment; identifying a sample suitable for saidexperiment; responsive to said receiving and said identifying, locatinga sample carrier supporting said sample on a discrete sample node;detecting a location of said discrete sample node on said samplecarrier; removing said discrete sample node from said sample carrier;and preparing said sample for analysis.
 78. The method of claim 77wherein said locating comprises interrogating a database maintainingrecords related to said sample carrier.
 79. The method of claim 77wherein said locating comprises utilizing an optical sensor.
 80. Themethod of claim 77 wherein said locating comprises reading a bar code.81. The method of claim 77 wherein said detecting comprises obtainingvideo signals output from an optical sensor.
 82. The method of claim 81wherein said removing comprises automatically operating a sample noderemoval device responsive to said obtaining video signals.
 83. Themethod of claim 81 wherein said removing comprises manually operating asample node removal device.
 84. The method of claim 77 wherein saiddetecting comprises identifying a unique signal transmitted from atransceiver attached to said discrete sample node.
 85. The method ofclaim 84 wherein said removing comprises transmitting a control signalto said transceiver.
 86. The method of claim 77 wherein said removingcomprises utilizing a laser.
 87. The method of claim 77 wherein saidremoving comprises utilizing a mechanical clipping tool.
 88. The methodof claim 77 wherein said preparing comprises depositing said discretesample node in a sample container.
 89. The method of claim 77 whereinsaid preparing comprises washing sample material attached to saiddiscrete sample node.
 90. The method of claim 77 wherein said sample isnon-biological.
 91. The method of claim 77 wherein said sample isbiological.
 92. The method of claim 91 wherein said sample is apolynucleotide.
 93. The method of claim 92 wherein said preparingcomprises amplifying said polynucleotide.
 94. A sample node removalsystem comprising: a sample carrier configured to support a plurality ofsample nodes in a predetermined spatial relationship; and node removalmeans for locating and removing selected ones of said plurality ofsample nodes.
 95. The system of claim 94 wherein said node removal meanscomprises a laser.
 96. The system of claim 94 wherein said node removalmeans comprises a mechanical clipping tool.
 97. The system of claim 94further comprising an optical component operative to detect the locationof said selected ones of said plurality of sample nodes.
 98. The systemof claim 97 further comprising a positioning component operative toposition said node removal means responsive to signals transmitted bysaid optical component.
 99. The system of claim 98 further comprising acomputer operative to receive said signals and to control saidpositioning component and said node removal means.
 100. The system ofclaim 95 wherein said sample node removal means further comprises amechanical positioning system to position said laser relative to saidselected ones of said plurality of sample nodes.
 101. The system ofclaim 96 wherein said sample node removal means further comprises amechanical positioning system to position said mechanical clipping toolrelative to said selected ones of said plurality of sample nodes.
 102. Amethod of preparing an archive sample for analysis; said methodcomprising: identifying a sample to be analyzed; responsive to saididentifying, obtaining said sample; preparing said sample for analysis;and selectively repeating said identifying, said obtaining, and saidpreparing at a rate sufficient to prepare in excess of 100 samples foranalysis per day.
 103. The method of claim 102 wherein said identifyingcomprises interrogating a database.
 104. The method of claim 102 whereinsaid identifying comprises utilizing an optical sensor.
 105. The methodof claim 102 wherein said obtaining comprises automatically operating asample node removal device.
 106. The method of claim 105 wherein saidobtaining comprises utilizing a laser.
 107. The method of claim 105wherein said obtaining comprises utilizing a mechanical clipping tool.108. The method of claim 102 wherein said preparing comprises depositingsaid sample in a sample container.
 109. The method of claim 102 whereinsaid preparing comprises washing said sample.
 110. The method of claim102 wherein said sample is non-biological.
 111. The method of claim 102wherein said sample is biological.
 112. The method of claim 111 whereinsaid sample is a polynucleotide.
 113. The method of claim 112 whereinsaid preparing comprises amplifying said polynucleotide.
 114. The methodof claim 111 wherein said selectively repeating occurs at a ratesufficient to prepare in excess of 200 samples for analysis per day.115. The method of claim 111 wherein said selectively repeating occursat a rate sufficient to prepare in excess of 500 samples for analysisper day.